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Type: Journal article
Title: Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution
Author: McWhorter, A.
Smith, L.
Masters, L.
Chan, B.
Shellam, G.
Redwood, A.
Citation: PLoS Pathogens, 2013; 9(1):e1003111-1-e1003111-13
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1553-7374
Editor: Mossman, K.L.
Statement of
Andrea R. McWhorter, Lee M. Smith, Laura L. Masters, Baca Chan, Geoffrey R. Shellam, Alec J. Redwood
Abstract: It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is common and has been linked to enhanced disease. Suggestions that disease enhancement in multi-strain infected patients is due to complementation have been supported by trans-complementation studies in mice during co-infection of wild type and gene knockout strains of murine CMV (MCMV). Complementation between naturally circulating strains of CMV has, however, not been assessed. In addition, many models of multi-strain infection predict that co-infecting strains will compete with each other and that this competition may contribute to selective transmission of more virulent pathogen strains. To assess the outcome of multi-strain infection, C57BL/6 mice were infected with up to four naturally circulating strains of MCMV. In this study, profound within-host competition was observed between co-infecting strains of MCMV. This competition was MCMV strain specific and resulted in the complete exclusion of certain strains of MCMV from the salivary glands of multi-strain infected mice. Competition was dependent on Ly49H(+) natural killer (NK) cells as well as the expression of the ligand for Ly49H, the MCMV encoded product, m157. Strains of MCMV which expressed an m157 gene product capable of ligating Ly49H were outcompeted by strains of MCMV expressing variant m157 genes. Importantly, within-host competition prevented the shedding of the less virulent strains of MCMV, those recognized by Ly49H, into the saliva of multi-strain infected mice. These data demonstrate that NK cells have the strain specific recognition capacity required to meditate within-host competition between strains of MCMV. Furthermore, this within-host competition has the capacity to shape the dynamics of viral shedding and potentially select for the transmission of more virulent virus strains.
Keywords: Animals
Mice, Inbred BALB C
Mice, Inbred C57BL
Salivary Glands
Cells, Cultured
Viral Proteins
Antibodies, Blocking
Antibodies, Monoclonal
Antigens, Viral
Lymphocyte Activation
Killer Cells, Natural
Mice, Transgenic
NK Cell Lectin-Like Receptor Subfamily A
Cytomegalovirus Infections
Rights: © 2013 McWhorter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.ppat.1003111
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Appears in Collections:Animal and Veterinary Sciences publications
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